Granulocyte colony-stimulating factor activation of Stat3 alpha and Stat3 beta in immature normal and leukemic human myeloid cells
| Autor: | A, Chakraborty, S M, White, T S, Schaefer, E D, Ball, K F, Dyer, D J, Tweardy |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
STAT3 Transcription Factor
Transcriptional Activation Base Sequence Gene Expression Regulation Leukemic Molecular Sequence Data Cell Differentiation Hematopoietic Stem Cells Neoplasm Proteins DNA-Binding Proteins Leukemia Myeloid Acute Disease Granulocyte Colony-Stimulating Factor Neoplastic Stem Cells Trans-Activators Tumor Cells Cultured Humans Amino Acid Sequence Signal Transduction |
| Zdroj: | Blood. 88(7) |
| ISSN: | 0006-4971 |
| Popis: | Granulocyte colony-stimulating factor (G-CSF) is the cytokine critical for directing neutrophilic granulocyte differentiation. Acute myelogenous leukemia (AML) cells, which frequently arise from this lineage, respond aberrantly to G-CSF by proliferating without differentiating. The basis for this abnormal responses is unknown. In the present study, we investigated whether G-CSF signaling in immature normal and leukemic human myeloid cells diverges at the level of activation of signal transducers and activators of transcription (STAT) proteins. We compared the profile of STAT proteins activated in G-CSF-stimulated immature normal and leukemic human myeloid cells. G-CSF activated Stat3 alpha in all AML cell lines examined except HL60 and in three of six uncultured AML patient samples. In normal human CD34+ bone marrow cells and HL60 cells, both reported to differentiate in response to G-CSF, G-CSF did not activate Stat3 alpha; rather, it activated only an 83 kD form of Stat3 that proved to be the human homologue of a short form of Stat3, Stat3 beta. Because the transcriptional activity of Stat3 beta is distinct from Stat3 alpha, these results suggest that the balance of the two Stat3 isoforms in myeloid cells may influence the cellular pattern of gene activation and consequently the ability of these cells to differentiate in response to G-CSF. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|